Scientists have made a breakthrough in protein synthesis by coaxing bacteria to incorporate structurally unusual amino acids into proteins. The conventional understanding is that DNA codes for 20 standard amino acids used in proteins, limiting the scope of protein design. However, researchers have now succeeded in adding four exotic building blocks, potentially expanding the palette for creating proteins. This development could lead to the production of medicines with prolonged effects in the body and improved catalysts for various industries.
The traditional method of engineering cells to produce proteins involves the use of living cells to achieve cost-effective protein synthesis. While researchers have managed to incorporate dozens of nonstandard but closely related alpha amino acids into proteins, there are hundreds of more exotic amino acids, such as beta and gamma varieties, which offer unique structural features. Until now, synthetic chemists have only added these exotic amino acids to proteins in test tubes.
The breakthrough involves two critical steps in protein synthesis: delivering amino acids to the ribosome (the cell's protein assembler) and stitching them onto a growing protein. Transfer RNA (tRNA) carries amino acids to the ribosome, and enzymes known as aminoacyl tRNA synthetases (aaRS) attach the proper amino acid to each tRNA. The loaded tRNAs then travel to the ribosome, where they link to corresponding sequences on messenger RNA (mRNA), facilitating the assembly of proteins.
The research team, led by Jason Chin and his colleagues at the U.K. Medical Research Council’s Laboratory of Molecular Biology, developed an innovative method to overcome the challenge of loading exotic amino acids onto tRNA. By mutating genes for aaRS enzymes, they created millions of alternative versions that might bind to exotic amino acids. They tagged each tRNA with an mRNA sequence of the altered enzymes and tracked which ones worked. The successful enzymes were then inserted into Escherichia coli bacteria, and the ribosomes successfully incorporated four exotic amino acids into growing protein chains.
This breakthrough could have significant implications, potentially allowing the design of protein-based drugs that resist degradation by enzymes in the body. Moreover, the use of exotic amino acids with different shapes could enhance industrial catalysts used in the production of pharmaceuticals and fuels. As the researchers continue to improve the process, they envision the engineering of bacteria to produce entirely new protein-like polymer materials composed of exotic amino acids, opening up possibilities for novel properties and applications.
More: https://www.science.org/content/article/bacteria-stitch-exotic-building-blocks-novel-proteins
